Increased formation of DNA adducts in cultured fibroblasts of patients with aplastic anemia after in vitro incubation with benzo(a)pyrene.
In inbred mice strain DBA/2, genetically controlled differences in aryl hydrocarbon hydroxylase (AHH) activity have been demonstrated that predispose to aplastic anemia. To test the hypothesis of a similar mechanism in humans, we studied the formation of benzo(a)pyrene DNA adducts and water-soluble metabolites in skin fibroblasts from eight patients with aplastic anemia and eight normal controls. The ratio of water-soluble metabolites and DNA adducts was 46.5 +/- 16.6 in patients and was significantly lower as compared to 82.9 +/- 38.5 in controls (P less than 0.05). We conclude that increased formation of genotoxic intermediates may be a pathogenetic mechanism in some patients with aplastic anemia.
Meyer
A
A
Krankenhaus Grosshansdorf, Zentrum für Pneumologie und Thoraxchirurgie, Federal Republic of Germany.
Nowak
D
D
Hossfeld
D
D
Rüdiger
H W
HW
D000328:Adult; D000368:Aged; D000741:Anemia, Aplastic / Q000209:etiology / Q000378:metabolism*; D001564:Benzo(a)pyrene / Q000494:pharmacology*; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis*; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D015262:Xenobiotics
D015262:Xenobiotics; D001564:Benzo(a)pyrene; D004247:DNA